tbuckley/cabot-search huggingface dataset:
Omalizumab in the treatment of bullous pemphigoid resistant to first-line therapy: a French national multicentre retrospective study of 100 patients
Authors: Réda Chebani, Florian Lombart, Guillaume Chaby, Ali Dadban, Sébastien Debarbieux, Manuelle-Anne Viguier, Saskia Ingen-Housz-Oro, Anne Pham-Ledard, Christophe R Bedane, Catherine Picard-Dahan, Clémence Berthin, Olivier Dereure, Maria-Polina Konstantinou, Marion Castel, Fabienne Jouen, Pascal Joly, Vannina Seta, Sophie Duvert-Lehembre, Christelle Le Roux, Gaëlle Quereux, Bruno Sassolas, Emilie Brenaut, Carole Sin, Marie-Aleth Richard, Frédéric Bérard, Delphine Giusti, Thibaut Belmondo, Thomas Gille, Frédéric Caux, Catherine Prost-Squarcioni, Sabine Grootenboer-Mignot, Marina Alexandre
Journal: British Journal of Dermatology (2023)

Abstract Background Interest in the use of omalizumab to treat bullous pemphigoid (BP) in the event of resistance or contraindication to conventional therapies is currently based on limited evidence. Objectives To assess the effectiveness and safety of omalizumab in BP and to identify predictive factors in response to treatment. Methods We conducted a French national multicentre retrospective study including patients with a confirmed diagnosis of BP treated with omalizumab after failure of one or several treatment lines. We excluded patients with clinically atypical BP, as per Vaillant’s criteria. The criteria for clinical response to omalizumab were defined according to the 2012 international consensus conference. Anti-BP180-NC16A IgE enzyme-linked immunosorbent assay was performed on sera collected before initiating omalizumab, when available. Results Between 2014 and 2021, 100 patients treated in 18 expert departments were included. Median age at diagnosis was 77 years (range 20–98). Complete remission (CR) was achieved in 77% of patients, and partial remission in an additional 9%. CR was maintained ‘off therapy’ in 11.7%, ‘on minimal therapy’ in 57.1%, and ‘on non-minimal therapy’ in 31.2%. Median time to CR was 3 months (range 2.2–24.5). Relapse rate was 14%, with a median follow-up time of 12 months (range 6–73). Adverse events occurred in four patients. CR was more frequently observed in patients with an increased serum baseline level of anti-BP180-NC16A IgE (75% vs. 41%; P = 0.011). Conversely, urticarial lesions, blood total IgE concentration or eosinophil count were not predictive of CR. Patients with an omalizumab dosage &amp;gt; 300 mg every 4 weeks showed a similar final outcome to those with a dosage ≤ 300 mg every 4 weeks, but control of disease activity [median 10 days (range 5–30) vs. 15 days (range 10–60); P &amp;lt; 0.001] and CR [median 2.4 months (range 2.2–8.2) vs. 3.9 months (range 2.3–24.5); P &amp;lt; 0.001] were achieved significantly faster. Conclusions We report the largest series to date of BP treated by omalizumab and confirm its effectiveness and safety in this indication. Serum baseline level of anti-BP180-NC16A IgE may predict response to treatment.
Mortality risks associated with floods in 761 communities worldwide: time series study
Authors: Zhengyu Yang, Wenzhong Huang, Joanne E McKenzie, Rongbin Xu, Pei Yu, Tingting Ye, Bo Wen, Antonio Gasparrini, Ben Armstrong, Shilu Tong, Eric Lavigne, Joana Madureira, Jan Kyselý, Yuming Guo, Shanshan Li
Journal: BMJ (2023)

To evaluate lag-response associations and effect modifications of exposure to floods with risks of all cause, cardiovascular, and respiratory mortality on a global scale.Time series study.761 communities in 35 countries or territories with at least one flood event during the study period.Multi-Country Multi-City Collaborative Research Network database, Australian Cause of Death Unit Record File, New Zealand Integrated Data Infrastructure, and the International Network for the Demographic Evaluation of Populations and their Health Network database.The main outcome was daily counts of deaths. An estimation for the lag-response association between flood and daily mortality risk was modelled, and the relative risks over the lag period were cumulated to calculate overall effects. Attributable fractions of mortality due to floods were further calculated. A quasi-Poisson model with a distributed lag non-linear function was used to examine how daily death risk was associated with flooded days in each community, and then the community specific associations were pooled using random effects multivariate meta-analyses. Flooded days were defined as days from the start date to the end date of flood events.A total of 47.6 million all cause deaths, 11.1 million cardiovascular deaths, and 4.9 million respiratory deaths were analysed. Over the 761 communities, mortality risks increased and persisted for up to 60 days (50 days for cardiovascular mortality) after a flooded day. The cumulative relative risks for all cause, cardiovascular, and respiratory mortality were 1.021 (95% confidence interval 1.006 to 1.036), 1.026 (1.005 to 1.047), and 1.049 (1.008 to 1.092), respectively. The associations varied across countries or territories and regions. The flood-mortality associations appeared to be modified by climate type and were stronger in low income countries and in populations with a low human development index or high proportion of older people. In communities impacted by flood, up to 0.10% of all cause deaths, 0.18% of cardiovascular deaths, and 0.41% of respiratory deaths were attributed to floods.This study found that the risks of all cause, cardiovascular, and respiratory mortality increased for up to 60 days after exposure to flood and the associations could vary by local climate type, socioeconomic status, and older age.
Progression of Pediatric Crohn’s Disease Is Associated With Anti–Tumor Necrosis Factor Timing and Body Mass Index Z-Score Normalization
Authors: Duke Geem, David Hercules, Ranjit S. Pelia, Suresh Venkateswaran, Anne Griffiths, Joshua D. Noe, Jennifer L. Dotson, Scott Snapper, Shervin Rabizadeh, Joel R. Rosh, Robert N. Baldassano, James F. Markowitz, Thomas D. Walters, Ashwin Ananthakrishnan, Garima Sharma, Lee A. Denson, Jeffrey S. Hyams, Subra Kugathasan
Journal: Clinical Gastroenterology and Hepatology (2023)
Disparities in cardiovascular disease and treatment in the Nordic countries
Authors: Signe Højstrup, Jakob Hartvig Thomsen, Eva Prescott
Journal: The Lancet Regional Health - Europe (2023)

The Nordic countries, including Denmark, Finland, Iceland, Norway, and Sweden have seen a steep decline in cardiovascular mortality in recent decades. They are among the most egalitarian countries by several measures, and all have universal, publicly funded welfare systems providing healthcare for all citizens. However, despite these seemingly ideal conditions, disparities in access to cardiovascular care and outcomes persist. To address this challenge, The Lancet Region Health—Europe convened experts from a broad range of countries to summarize the current state of knowledge on cardiovascular disease disparities across Europe. This Series Paper presents the main challenges in Nordic countries based on evidence from high-quality nationwide registries. Focusing on major cardiovascular health determinants, areas in need of improvement were identified. There is a need for addressing structural causes underlying these disparities, such as poverty and discrimination, but also to improve access to healthcare in deprived neighborhoods and to address underlying social determinants of health that may mitigate disparities in cardiovascular outcomes. Overall, while the Nordic countries have made great strides in promoting egalitarianism and providing universal healthcare, there is still much work to be done to ensure equitable access to care and improved cardiovascular outcomes for all members of society.
Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis
Authors: Cong Liu, Renjie Chen, Francesco Sera, Ana Maria Vicedo-Cabrera, Yuming Guo, Shilu Tong, Eric Lavigne, Patricia Matus Correa, Nicolás Valdés Ortega, Souzana Achilleos, Dominic Roye, Jouni JK Jaakkola, Niilo Ryti, Mathilde Pascal, Alexandra Schneider, Susanne Breitner, Alireza Entezari, Fatemeh Mayvaneh, Raanan Raz, Yasushi Honda, Masahiro Hashizume, Chris Fook Sheng Ng, Vânia Gaio, Joana Madureira, Iulian-Horia Holobaca, Aurelio Tobias, Carmen Íñiguez, Yue Leon Guo, Shih-Chun Pan, Pierre Masselot, Michelle L Bell, Antonella Zanobetti, Joel Schwartz, Antonio Gasparrini, Haidong Kan
Journal: BMJ (2023)

To investigate potential interactive effects of fine particulate matter (PM
Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial
Authors: Magdalena E Sobieszczyk, Sharon Mannheimer, Carmen A Paez, Chenchen Yu, Theresa Gamble, Deborah A Theodore, Wairimu Chege, Margaret Yacovone, Brett Hanscom, Jack Heptinstall, Kelly E Seaton, Lily Zhang, Maurine D Miner, Amanda Eaton, Joshua A Weiner, Kenneth Mayer, Spyros Kalams, Kathryn Stephenson, Boris Julg, Marina Caskey, Michel Nussenzweig, Lucio Gama, Dan H Barouch, Margaret E Ackerman, Georgia D Tomaras, Yunda Huang, David Montefiori
Journal: The Lancet HIV (2023)
Interval post-colonoscopy colorectal cancer following a negative colonoscopy in a fecal immunochemical test-based screening program
Authors: Hilliene J. van de Schootbrugge-Vandermeer, Arthur I. Kooyker, Manon C. W. Spaander, Monique E. van Leerdam, Pieter H. A. Wisse, Iris D. Nagtegaal, Hiltje A. Geuzinge, Esther Toes-Zoutendijk, Lucie de Jonge, Emilie C. H. Breekveldt, Anneke J. van Vuuren, Folkert J. van Kemenade, Christian R. B. Ramakers, Evelien Dekker, Iris Lansdorp-Vogelaar
Journal: Endoscopy (2023)

Background In the Dutch colorectal (CRC) screening program, fecal immunochemical test (FIT)-positive individuals are referred for colonoscopy. If no relevant findings are detected at colonoscopy, individuals are reinvited for FIT screening after 10 years. We aimed to assess CRC risk after a negative colonoscopy in FIT-positive individuals. Methods In this cross-sectional cohort study, data were extracted from the Dutch national screening information system. Participants with a positive FIT followed by a negative colonoscopy between 2014 and 2018 were included. A negative colonoscopy was defined as a colonoscopy during which no more than one nonvillous, nonproximal adenoma &lt; 10 mm or serrated polyp &lt; 10 mm was found. The main outcome was interval post-colonoscopy CRC (iPCCRC) risk. iPCCRC risk was reviewed against the risk of interval CRC after a negative FIT (FIT IC) with a 2-year screening interval. Results 35 052 FIT-positive participants had a negative colonoscopy and 24 iPCCRCs were diagnosed, resulting in an iPCCRC risk of 6.85 (95 %CI 4.60–10.19) per 10 000 individuals after a median follow-up of 1.4 years. After 2.5 years of follow-up, age-adjusted iPCCRC risk was approximately equal to FIT IC risk at 2 years. Conclusion Risk of iPCCRC within a FIT-based CRC screening program was low during the first years after colonos-copy but, after 2.5 years, was the same as the risk in FIT-negative individuals at 2 years, when they are reinvited for screening. Colonoscopy quality may therefore require further improvement and FIT screening interval may need to be reduced after negative colonoscopy.
Impact of differentiated service delivery models on 12-month retention in HIV treatment in Mozambique: an interrupted time-series analysis
Authors: Dorlim A Moiana Uetela, Orvalho Augusto, James P Hughes, Onei A Uetela, Eduardo Samo Gudo, Sérgio A Chicumbe, Aleny M Couto, Irénio A Gaspar, Diogo L Chavana, Sandra E Gaveta, Marita R Zimmermann, Sarah Gimbel, Kenneth Sherr
Journal: The Lancet HIV (2023)
Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis
Authors: Jemma Hudson, Moira Cruickshank, Richard Quinton, Lorna Aucott, Frederick Wu, Mathis Grossmann, Shalender Bhasin, Peter J Snyder, Susan S Ellenberg, Thomas G Travison, Gerald B Brock, Emily J Gianatti, Yvonne T van der Schouw, Marielle H Emmelot-Vonk, Erik J Giltay, Geoff Hackett, Sudarshan Ramachandran, Johan Svartberg, Kerry L Hildreth, Kristina Groti Antonic, Joyce Lisa Tenover, Hui Meng Tan, Christopher Ho Chee Kong, Wei Shen Tan, Leonard S Marks, Richard J Ross, Robert S Schwartz, Paul Manson, Stephen A Roberts, Marianne Skovsager Andersen, Line Velling Magnussen, Magaly Aceves-Martins, Katie Gillies, Rodolfo Hernández, Nick Oliver, Waljit S Dhillo, Siladitya Bhattacharya, Miriam Brazzelli, Channa N Jayasena
Journal: The Lancet Healthy Longevity (2023)

Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment.
Faster-acting insulin aspart versus insulin aspart in the treatment of type 1 or type 2 diabetes during pregnancy and post-delivery (CopenFast): an open-label, single-centre, randomised controlled trial
Authors: Sidse K Nørgaard, Julie C Søholm, Elisabeth R Mathiesen, Kirsten Nørgaard, Tine D Clausen, Pernille Holmager, Nicoline C Do, Peter Damm, Lene Ringholm
Journal: The Lancet Diabetes & Endocrinology (2023)
Healthy lifestyle in late-life, longevity genes, and life expectancy among older adults: a 20-year, population-based, prospective cohort study
Authors: Jun Wang, Chen Chen, Jinhui Zhou, Lihong Ye, Yang Li, Lanjing Xu, Zinan Xu, Xinwei Li, Yuan Wei, Junxin Liu, Yuebin Lv, Xiaoming Shi
Journal: The Lancet Healthy Longevity (2023)

BackgroundLifestyle and longevity genes have different and important roles in the human lifespan; however, the association between a healthy lifestyle in late-life and life expectancy mediated by genetic risk is yet to be elucidated. We aimed to investigate the associations of healthy lifestyle in late-life and genetic risk with life expectancy among older adults.MethodsA weighted healthy lifestyle score was constructed from the following variables: current non-smoking, non-harmful alcohol consumption, regular physical activity, and a healthy diet. Participants were recruited from the Chinese Longitudinal Healthy Longevity Survey, a prospective community-based cohort study that took place between 1998 and 2018. Eligible participants were aged 65 years and older with available information on lifestyle factors at baseline, and then were categorised into unhealthy (bottom tertile of the weighted healthy lifestyle score), intermediate (middle tertile), and healthy (top tertile) lifestyle groups. A genetic risk score was constructed based on 11 lifespan loci among 9633 participants, divided by the median and classified into low and high genetic risk groups. Stratified Cox proportional hazard regression was used to estimate the interaction between genetic and lifestyle factors on all-cause mortality risk.FindingsBetween Jan 13, 1998, and Dec 31, 2018, 36 164 adults aged 65 years and older were recruited, among whom a total of 27 462 deaths were documented during a median follow-up of 3·12 years (IQR 1·62–5·94) and included in the lifestyle association analysis. Compared with the unhealthy lifestyle category, participants in the healthy lifestyle group had a lower all-cause mortality risk (hazard ratio [HR] 0·56 [95% CI 0·54–0·57]; p<0·0001). The highest mortality risk was observed in individuals in the high genetic risk and unhealthy lifestyle group (HR 1·80 [95% CI 1·63–1·98]; p<0·0001). The absolute risk reduction was greater for participants in the high genetic risk group. A healthy lifestyle was associated with a gain of 3·84 years (95% CI 3·05–4·64) at the age of 65 years in the low genetic risk group, and 4·35 years (3·70–5·06) in the high genetic risk group.InterpretationA healthy lifestyle, even in late-life, was associated with lower mortality risk and longer life expectancy among Chinese older adults, highlighting the importance of a healthy lifestyle in extending the lifespan, especially for individuals with high genetic risk.FundingNational Natural Science Foundation of China.TranslationFor the Mandarin translation of the abstract see Supplementary Materials section.
Coordinating Efforts to Reduce the Global Incidence of Cardiovascular Disease
Authors: Philip Joseph, Salim Yusuf
Journal: New England Journal of Medicine (2023)

One third of deaths worldwide are due to cardiovascular diseases. Understanding the extent to which the incidence of cardiovascular disease and risk-factor burden differ across the world is useful to inform local and global health policies, although comparable data from various world regions are sparse. Most reported studies of risk factors for cardiovascular disease have been from high-income, Western countries, with few data from other regions of the world. In this issue of the Journal, Magnussen et al. report the results of a study investigating cardiovascular risk factors and their associated population-attributable fractions of the incidence of cardiovascular disease and . . .
Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper
Authors: Robert F. Spiera, Sebastian Unizony, Kenneth J. Warrington, Jennifer Sloane, Angeliki Giannelou, Michael C. Nivens, Bolanle Akinlade, Wanling Wong, Rafia Bhore, Yong Lin, Frank Buttgereit, Valerie Devauchelle-Pensec, Andrea Rubbert-Roth, George D. Yancopoulos, Frederic Marrache, Naimish Patel, Bhaskar Dasgupta
Journal: New England Journal of Medicine (2023)

More than half of patients with polymyalgia rheumatica have a relapse during tapering of glucocorticoid therapy. Previous studies have suggested that interleukin-6 blockade may be clinically useful in the treatment of polymyalgia rheumatica. Sarilumab, a human monoclonal antibody, binds interleukin-6 receptor α and efficiently blocks the interleukin-6 pathway.In this phase 3 trial, we randomly assigned patients in a 1:1 ratio to receive 52 weeks of a twice-monthly subcutaneous injection of either sarilumab (at a dose of 200 mg) plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. The primary outcome at 52 weeks was sustained remission, which was defined as the resolution of signs and symptoms of polymyalgia rheumatica by week 12 and sustained normalization of the C-reactive protein level, absence of disease flare, and adherence to the prednisone taper from weeks 12 through 52.A total of 118 patients underwent randomization (60 to receive sarilumab and 58 to receive placebo). At week 52, sustained remission occurred in 28% (17 of 60 patients) in the sarilumab group and in 10% (6 of 58 patients) in the placebo group (difference, 18 percentage points; 95% confidence interval, 4 to 32; P = 0.02). The median cumulative glucocorticoid dose at 52 weeks was significantly lower in the sarilumab group than in the placebo group (777 mg vs. 2044 mg; P<0.001). The most common adverse events with sarilumab as compared with placebo were neutropenia (15% vs. 0%), arthralgia (15% vs. 5%), and diarrhea (12% vs. 2%). More treatment-related discontinuations were observed in the sarilumab group than in the placebo group (12% vs. 7%).Sarilumab showed significant efficacy in achieving sustained remission and reducing the cumulative glucocorticoid dose in patients with a relapse of polymyalgia rheumatica during glucocorticoid tapering. (Funded by Sanofi and Regeneron Pharmaceuticals; SAPHYR ClinicalTrials.gov number, NCT03600818.).
Polymyalgia Rheumatica — from Search for Efficacy to Choice of Strategy
Authors: Daniel Aletaha
Journal: New England Journal of Medicine (2023)

Clinicians may have an ambivalent attitude about polymyalgia rheumatica, a disabling disease marked by severe muscle pain and stiffness. On the one hand, it is most rewarding to be able to almost magically "cure" many patients within days after the start of glucocorticoid therapy. On the other hand, despite this prompt response, such therapy is actually not a cure for most patients. Relapse and dependence on glucocorticoids are major therapeutic challenges.1 Strategies to maintain this initial response over longer periods of time while successfully tapering the dose of glucocorticoids have been limited. Evidence regarding therapies that may reduce the need . . .
Mutations in the histone methyltransferase Ezh2 drive context-dependent leukemia in Xenopus tropicalis
Authors: Dieter Tulkens, Marthe Boelens, Thomas Naert, Marjolein Carron, Suzan Demuynck, Sylviane Dewaele, Gert Van Isterdael, David Creytens, Tim Pieters, Steven Goossens, Pieter Van Vlierberghe, Kris Vleminckx
Journal: Leukemia (2023)
Digging into the Histology
Authors: Raghavendra Paknikar, Lindsay Alpert, Russell D. Cohen, Benjamin Shogan, Dejan Micic
Journal: New England Journal of Medicine (2023)

A 33-year-old man with ulcerative colitis presented with bloody diarrhea, an 8-month history of worsening fatigue and diarrhea, and a 4-month history of fevers, drenching night sweats, and unintentional weight loss.
Loosening the Shackles of Depression
Authors: Rupert McShane
Journal: New England Journal of Medicine (2023)

Depression can become self-perpetuating as occupational, relationship, and social losses accrue. Sustained remission is achieved in less than half of patients taking a first antidepressant agent,1 and guidance on what to prescribe after treatment with a second antidepressant agent fails is inconsistent, reflecting the wide choice of possibilities and the small differences among them. Of the options, the addition of an atypical antipsychotic agent has had the most support.2 In this issue of the Journal, Reif et al.3 report the results of the ESCAPE-TRD trial, a head-to-head comparison of esketamine nasal spray with extended-release quetiapine in the treatment of 676 . . .
MyPathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab + Trastuzumab Treatment of a Tissue-Agnostic Cohort of Patients With Human Epidermal Growth Factor Receptor 2–Altered Advanced Solid Tumors
Authors: Christopher J. Sweeney, John D. Hainsworth, Ron Bose, Howard A. Burris, Razelle Kurzrock, Charles Swanton, Claire F. Friedman, David R. Spigel, Tania Szado, Katja Schulze, Richard Price, Julia Malato, Amy A. Lo, Jonathan Levy, Yong Wang, Wei Yu, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2023)

JCO
Takeda K, Cretney E, Hayakawa Y, Ota T, Akiba H, Ogasawara K, Yagita H, Kinoshita K, Okumura K, Smyth MJ. TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver. <i>Blood.</i> 2005;105(5):2082-2089.
Journal: Blood (2023)
Updating cancer research with patient-focused networks
Authors: Manuel Valiente, Eva Ortega-Paino
Journal: Trends in cancer (2023)

Multidisciplinary patient-centered networks offer access to difficult-to-get samples and initiate projects from human material. Improving such networks to include 'living' samples could be transformative, not only for research but for clinical trial design, especially when focused on unmet clinical needs, such as brain metastasis.